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01-09-2018 | Review

Extracellular vesicles in cancer immune responses: roles of purinergic receptors

Author: Michael W Graner

Published in: Seminars in Immunopathology | Issue 5/2018

Abstract

Extracellular vesicles (EVs) are nano- to micro-scale membrane-enclosed vesicles that are released from presumably all cell types. Tumor cells and immune cells are prodigious generators of EVs often with competing phenotypes in terms of immune suppression versus immune stimulation. Purinergic receptors, proteins that bind diverse purine nucleotides and nucleosides (ATP, ADP, AMP, adenosine), are widely expressed across tissues and cell types, and are prominent players in immune and tumor cell nucleotide metabolism. The effects of purinergic receptor stimulation or agonism tend to produce inflammatory responses that may aid immune stimulation but may also provoke various immune suppression mechanisms, particularly in the tumor microenvironment. EVs released by cells following receptor stimulation are frequently pro-inflammatory, but often also pro-thrombolytic; these EVs may generate an environment that favors tumor progression at the cost of an effective immune response. Purinergic signaling pathways are becoming more recognized as valuable targets in various therapeutic scenarios, including cancer. It is possible that some of those clinically relevant compounds might also impact EV secretion and/or phenotype, which would hopefully capitalize on the immune stimulatory properties of purinergic signaling while minimizing the immune suppressive consequences. This review covers a relatively understudied area in EV biology, but even so, focuses almost exclusively on the purinergic receptors in a very limited capacity. There is much more to evaluate and incorporate into our understanding of extracellular nucleotides in EV biology, and we hope this work prompts further discovery.

Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Kramer-Albers EM, Laitinen S, Lasser C, Lener T, Ligeti E, Line A, Lipps G, Llorente A, Lotvall J, Mancek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-'t Hoen EN, Nyman TA, O'Driscoll L, Olivan M, Oliveira C, Pallinger E, Del Portillo HA, Reventos J, Rigau M, Rohde E, Sammar M, Sanchez-Madrid F, Santarem N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066. https://doi.org/10.3402/jev.v4.27066 CrossRefPubMed

De Toro J, Herschlik L, Waldner C, Mongini C (2015) Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol 6:203. https://doi.org/10.3389/fimmu.2015.00203 CrossRefPubMedPubMedCentral

Benito-Martin A, Di Giannatale A, Ceder S, Peinado H (2015) The new deal: a potential role for secreted vesicles in innate immunity and tumor progression. Front Immunol 6:66. https://doi.org/10.3389/fimmu.2015.00066 CrossRefPubMedPubMedCentral

Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W (2015) Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 40:72–81. https://doi.org/10.1016/j.semcdb.2015.02.009 CrossRefPubMed

Hellwinkel JE, Madsen H, Graner MW (2015) Immune modulation by tumor-derived extracellular vesicles in glioblastoma. Molecular considerations and evolving surgical management issues in the treatment of patients with a brain tumor. In: InTech, Rijeka. https://doi.org/10.5772/59037

Camisaschi C, Vallacchi V, Vergani E, Tazzari M, Ferro S, Tuccitto A, Kuchuk O, Shahaj E, Sulsenti R, Castelli C, Rodolfo M, Rivoltini L, Huber V (2016) Targeting immune regulatory networks to counteract immune suppression in cancer. Vaccines (Basel) 4(4). https://doi.org/10.3390/vaccines4040038 CrossRefPubMedCentral

Kunigelis KE, Graner MW (2015) The dichotomy of tumor exosomes (TEX) in cancer immunity: is it all in the ConTEXt? Vaccines (Basel) 3(4):1019–1051. https://doi.org/10.3390/vaccines3041019 CrossRef

Wen C, Seeger RC, Fabbri M, Wang L, Wayne AS, Jong AY (2017) Biological roles and potential applications of immune cell-derived extracellular vesicles. J Extracell Vesicles 6(1):1400370. https://doi.org/10.1080/20013078.2017.1400370 CrossRefPubMedPubMedCentral

De Robertis ED, Bennett HS (1955) Some features of the submicroscopic morphology of synapses in frog and earthworm. J Biophys Biochem Cytol 1(1):47–58CrossRefPubMedCentral

10.

Monleon I, Martinez-Lorenzo MJ, Monteagudo L, Lasierra P, Taules M, Iturralde M, Pineiro A, Larrad L, Alava MA, Naval J, Anel A (2001) Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells. J Immunol 167(12):6736–6744CrossRefPubMed

11.

Zuccato E, Blott EJ, Holt O, Sigismund S, Shaw M, Bossi G, Griffiths GM (2007) Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation. J Cell Sci 120(Pt 1):191–199. https://doi.org/10.1242/jcs.03315 CrossRefPubMed

12.

Brody I, Ronquist G, Gottfries A (1983) Ultrastructural localization of the prostasome—an organelle in human seminal plasma. Ups J Med Sci 88(2):63–80CrossRefPubMed

13.

Bilen MA, Pan T, Lee YC, Lin SC, Yu G, Pan J, Hawke D, Pan BF, Vykoukal J, Gray K, Satcher RL, Gallick GE, Yu-Lee LY, Lin SH (2017) Proteomics profiling of exosomes from primary mouse osteoblasts under proliferation versus mineralization conditions and characterization of their uptake into prostate cancer cells. J Proteome Res 16(8):2709–2728. https://doi.org/10.1021/acs.jproteome.6b00981 CrossRefPubMedPubMedCentral

14.

Greco V, Hannus M, Eaton S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106(5):633–645CrossRefPubMed

15.

Lee TH, D'Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J (2011) Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’. Semin Immunopathol 33(5):455–467. https://doi.org/10.1007/s00281-011-0250-3 CrossRefPubMed

16.

Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262(19):9412–9420PubMed

17.

Piper RC, Luzio JP (2001) Late endosomes: sorting and partitioning in multivesicular bodies. Traffic 2(9):612–621CrossRefPubMed

18.

Gould SJ, Raposo G (2013) As we wait: coping with an imperfect nomenclature for extracellular vesicles. J Extracell Vesicles 2. https://doi.org/10.3402/jev.v2i0.20389 CrossRef

19.

Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific CM, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferreira JA, Osorio H, Silva AM, Massey A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D (2018) Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 20(3):332–343. https://doi.org/10.1038/s41556-018-0040-4 CrossRefPubMedPubMedCentral

20.

Gyorgy B, Szabo TG, Pasztoi M, Pal Z, Misjak P, Aradi B, Laszlo V, Pallinger E, Pap E, Kittel A, Nagy G, Falus A, Buzas EI (2011) Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 68(16):2667–2688. https://doi.org/10.1007/s00018-011-0689-3 CrossRefPubMedPubMedCentral

21.

Xu R, Greening DW, Rai A, Ji H, Simpson RJ (2015) Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Methods 87:11–25. https://doi.org/10.1016/j.ymeth.2015.04.008 CrossRefPubMed

22.

Jeppesen DK, Hvam ML, Primdahl-Bengtson B, Boysen AT, Whitehead B, Dyrskjot L, Orntoft TF, Howard KA, Ostenfeld MS (2014) Comparative analysis of discrete exosome fractions obtained by differential centrifugation. J Extracell Vesicles 3:25011. https://doi.org/10.3402/jev.v3.25011 CrossRefPubMed

23.

Willms E, Johansson HJ, Mager I, Lee Y, Blomberg KE, Sadik M, Alaarg A, Smith CI, Lehtio J, El Andaloussi S, Wood MJ, Vader P (2016) Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep 6:22519. https://doi.org/10.1038/srep22519 CrossRefPubMedPubMedCentral

24.

Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Thery C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A 113(8):E968–E977. https://doi.org/10.1073/pnas.1521230113 CrossRefPubMedPubMedCentral

25.

Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23(5):1541–1557. https://doi.org/10.1096/fj.08-122184 CrossRefPubMedPubMedCentral

26.

Griffiths SG, Cormier MT, Clayton A, Doucette AA (2017) Differential proteome analysis of extracellular vesicles from breast cancer cell lines by chaperone affinity enrichment. Proteomes 5(4). https://doi.org/10.3390/proteomes5040025 CrossRefPubMedCentral

27.

Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7(3):297–303CrossRefPubMed

28.

Altieri SL, Khan AN, Tomasi TB (2004) Exosomes from plasmacytoma cells as a tumor vaccine. J Immunother 27(4):282–288CrossRefPubMed

29.

Whiteside TL (2017a) Exosomes in cancer: another mechanism of tumor-induced immune suppression. Adv Exp Med Biol 1036:81–89. https://doi.org/10.1007/978-3-319-67577-0_6 CrossRefPubMed

30.

Czernek L, Duchler M (2017) Functions of cancer-derived extracellular vesicles in immunosuppression. Arch Immunol Ther Exp 65(4):311–323. https://doi.org/10.1007/s00005-016-0453-3 CrossRef

31.

Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, Li G (2008) Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther 16(4):782–790. https://doi.org/10.1038/mt.2008.1 CrossRefPubMed

32.

Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD (2001) Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol 19(8):2189–2200. https://doi.org/10.1200/JCO.2001.19.8.2189 CrossRefPubMed

33.

Harshyne LA, Hooper KM, Andrews EG, Nasca BJ, Kenyon LC, Andrews DW, Hooper DC (2015) Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm. Cancer Immunol Immunother 64(3):299–309. https://doi.org/10.1007/s00262-014-1622-z CrossRefPubMed

34.

Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, Le Chevalier T, Livartoski A, Barlesi F, Laplanche A, Ploix S, Vimond N, Peguillet I, Thery C, Lacroix L, Zoernig I, Dhodapkar K, Dhodapkar M, Viaud S, Soria JC, Reiners KS, Pogge von Strandmann E, Vely F, Rusakiewicz S, Eggermont A, Pitt JM, Zitvogel L, Chaput N (2016) Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 5(4):e1071008. https://doi.org/10.1080/2162402X.2015.1071008 CrossRefPubMed

35.

Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq JB, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med 3(1):10CrossRefPubMedPubMedCentral

36.

Whiteside TL (2016) Exosomes and tumor-mediated immune suppression. J Clin Invest 126(4):1216–1223. https://doi.org/10.1172/JCI81136 CrossRefPubMedPubMedCentral

37.

Whiteside TL (2017b) Exosomes carrying immunoinhibitory proteins and their role in cancer. Clin Exp Immunol 189(3):259–267. https://doi.org/10.1111/cei.12974 CrossRefPubMedPubMedCentral

38.

Chen W, Jiang J, Xia W, Huang J (2017) Tumor-related exosomes contribute to tumor-promoting microenvironment: an immunological perspective. J Immunol Res 2017:1073947. https://doi.org/10.1155/2017/1073947 CrossRefPubMedPubMedCentral

39.

Qu X, Tang Y, Hua S (2018) Immunological approaches towards cancer and inflammation: a cross talk. Front Immunol 9:563. https://doi.org/10.3389/fimmu.2018.00563 CrossRefPubMedPubMedCentral

40.

Idzko M, Ferrari D, Eltzschig HK (2014) Nucleotide signalling during inflammation. Nature 509(7500):310–317. https://doi.org/10.1038/nature13085 CrossRefPubMedPubMedCentral

41.

Roger S, Jelassi B, Couillin I, Pelegrin P, Besson P, Jiang LH (2015) Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives. Biochim Biophys Acta 1848(10 Pt B):2584–2602. https://doi.org/10.1016/j.bbamem.2014.10.029 CrossRefPubMed

42.

Burnstock G (2017) Purinergic signalling: therapeutic developments. Front Pharmacol 8:661. https://doi.org/10.3389/fphar.2017.00661 CrossRefPubMedPubMedCentral

43.

Di Virgilio F, Adinolfi E (2017) Extracellular purines, purinergic receptors and tumor growth. Oncogene 36(3):293–303. https://doi.org/10.1038/onc.2016.206 CrossRefPubMed

44.

Williams M, Jarvis MF (2000) Purinergic and pyrimidinergic receptors as potential drug targets. Biochem Pharmacol 59(10):1173–1185CrossRefPubMed

45.

Yegutkin GG (2014) Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities. Crit Rev Biochem Mol Biol 49(6):473–497. https://doi.org/10.3109/10409238.2014.953627 CrossRefPubMed

46.

Falzoni S, Donvito G, Di Virgilio F (2013) Detecting adenosine triphosphate in the pericellular space. Interface Focus 3(3):20120101. https://doi.org/10.1098/rsfs.2012.0101 CrossRefPubMedPubMedCentral

47.

Lazarowski ER (2012) Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal 8(3):359–373. https://doi.org/10.1007/s11302-012-9304-9 CrossRefPubMedPubMedCentral

48.

Burnstock G (2018) The therapeutic potential of purinergic signalling. Biochem Pharmacol 151:157–165. https://doi.org/10.1016/j.bcp.2017.07.016 CrossRefPubMed

49.

Burnstock G (2014) Purinergic signalling: from discovery to current developments. Exp Physiol 99(1):16–34. https://doi.org/10.1113/expphysiol.2013.071951 CrossRefPubMed

50.

Fredholm BB, AP IJ, Jacobson KA, Linden J, Muller CE (2011) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev 63(1):1–34. https://doi.org/10.1124/pr.110.003285 CrossRefPubMedPubMedCentral

51.

North RA (2016) P2X receptors. Philos Trans R Soc Lond Ser B Biol Sci 371(1700):20150427. https://doi.org/10.1098/rstb.2015.0427 CrossRef

52.

Hasko G, Antonioli L, Cronstein BN (2018) Adenosine metabolism, immunity and joint health. Biochem Pharmacol 151:307–313. https://doi.org/10.1016/j.bcp.2018.02.002 CrossRefPubMedPubMedCentral

53.

Satoh T, Otsuka A, Contassot E, French LE (2015) The inflammasome and IL-1beta: implications for the treatment of inflammatory diseases. Immunotherapy 7(3):243–254. https://doi.org/10.2217/imt.14.106 CrossRefPubMed

54.

Lopez-Castejon G, Brough D (2011) Understanding the mechanism of IL-1beta secretion. Cytokine Growth Factor Rev 22(4):189–195. https://doi.org/10.1016/j.cytogfr.2011.10.001 CrossRefPubMedPubMedCentral

55.

Dubyak GR (2012) P2X7 receptor regulation of non-classical secretion from immune effector cells. Cell Microbiol 14(11):1697–1706. https://doi.org/10.1111/cmi.12001 CrossRefPubMedPubMedCentral

56.

MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, Surprenant A (2001) Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 15(5):825–835CrossRefPubMed

57.

Li Q, Barres BA (2018) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol 18(4):225–242. https://doi.org/10.1038/nri.2017.125 CrossRefPubMed

58.

Bianco F, Pravettoni E, Colombo A, Schenk U, Moller T, Matteoli M, Verderio C (2005) Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J Immunol 174(11):7268–7277CrossRefPubMed

59.

Bianco F, Perrotta C, Novellino L, Francolini M, Riganti L, Menna E, Saglietti L, Schuchman EH, Furlan R, Clementi E, Matteoli M, Verderio C (2009) Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28(8):1043–1054. https://doi.org/10.1038/emboj.2009.45 CrossRefPubMedPubMedCentral

60.

Bowser DN, Khakh BS (2007) Vesicular ATP is the predominant cause of intercellular calcium waves in astrocytes. J Gen Physiol 129(6):485–491. https://doi.org/10.1085/jgp.200709780 CrossRefPubMedPubMedCentral

61.

Moro S, Guo D, Camaioni E, Boyer JL, Harden TK, Jacobson KA (1998) Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites. J Med Chem 41(9):1456–1466. https://doi.org/10.1021/jm970684u CrossRefPubMedPubMedCentral

62.

Sakaki H, Tsukimoto M, Harada H, Moriyama Y, Kojima S (2013) Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor. PLoS One 8(4):e59778. https://doi.org/10.1371/journal.pone.0059778 CrossRefPubMedPubMedCentral

63.

Murray PJ (2017) Macrophage polarization. Annu Rev Physiol 79:541–566. https://doi.org/10.1146/annurev-physiol-022516-034339 CrossRefPubMed

64.

Pizzirani C, Ferrari D, Chiozzi P, Adinolfi E, Sandona D, Savaglio E, Di Virgilio F (2007) Stimulation of P2 receptors causes release of IL-1beta-loaded microvesicles from human dendritic cells. Blood 109(9):3856–3864. https://doi.org/10.1182/blood-2005-06-031377 CrossRefPubMed

65.

Baroni M, Pizzirani C, Pinotti M, Ferrari D, Adinolfi E, Calzavarini S, Caruso P, Bernardi F, Di Virgilio F (2007) Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor-bearing microparticles. FASEB J 21(8):1926–1933. https://doi.org/10.1096/fj.06-7238com CrossRefPubMed

66.

Qu Y, Franchi L, Nunez G, Dubyak GR (2007) Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 179(3):1913–1925CrossRefPubMed

67.

Qu Y, Ramachandra L, Mohr S, Franchi L, Harding CV, Nunez G, Dubyak GR (2009) P2X7 receptor-stimulated secretion of MHC class II-containing exosomes requires the ASC/NLRP3 inflammasome but is independent of caspase-1. J Immunol 182(8):5052–5062. https://doi.org/10.4049/jimmunol.0802968 CrossRefPubMed

68.

Rothmeier AS, Marchese P, Petrich BG, Furlan-Freguia C, Ginsberg MH, Ruggeri ZM, Ruf W (2015) Caspase-1-mediated pathway promotes generation of thromboinflammatory microparticles. J Clin Invest 125(4):1471–1484. https://doi.org/10.1172/JCI79329 CrossRefPubMedPubMedCentral

69.

Novick D, Kim S, Kaplanski G, Dinarello CA (2013) Interleukin-18, more than a Th1 cytokine. Semin Immunol 25(6):439–448. https://doi.org/10.1016/j.smim.2013.10.014 CrossRefPubMed

70.

Gulinelli S, Salaro E, Vuerich M, Bozzato D, Pizzirani C, Bolognesi G, Idzko M, Di Virgilio F, Ferrari D (2012) IL-18 associates to microvesicles shed from human macrophages by a LPS/TLR-4 independent mechanism in response to P2X receptor stimulation. Eur J Immunol 42(12):3334–3345. https://doi.org/10.1002/eji.201142268 CrossRefPubMed

71.

Thomas LM, Salter RD (2010) Activation of macrophages by P2X7-induced microvesicles from myeloid cells is mediated by phospholipids and is partially dependent on TLR4. J Immunol 185(6):3740–3749. https://doi.org/10.4049/jimmunol.1001231 CrossRefPubMed

72.

Barbera-Cremades M, Gomez AI, Baroja-Mazo A, Martinez-Alarcon L, Martinez CM, de Torre-Minguela C, Pelegrin P (2017) P2X7 receptor induces tumor necrosis factor-alpha converting enzyme activation and release to boost TNF-alpha production. Front Immunol 8:862. https://doi.org/10.3389/fimmu.2017.00862 CrossRefPubMedPubMedCentral

73.

Aymeric L, Apetoh L, Ghiringhelli F, Tesniere A, Martins I, Kroemer G, Smyth MJ, Zitvogel L (2010) Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 70(3):855–858. https://doi.org/10.1158/0008-5472.CAN-09-3566 CrossRefPubMed

74.

Di Virgilio F, Vuerich M (2015) Purinergic signaling in the immune system. Auton Neurosci 191:117–123. https://doi.org/10.1016/j.autneu.2015.04.011 CrossRefPubMed

75.

la Sala A, Sebastiani S, Ferrari D, Di Virgilio F, Idzko M, Norgauer J, Girolomoni G (2002) Dendritic cells exposed to extracellular adenosine triphosphate acquire the migratory properties of mature cells and show a reduced capacity to attract type 1 T lymphocytes. Blood 99(5):1715–1722CrossRefPubMed

76.

Frascoli M, Marcandalli J, Schenk U, Grassi F (2012) Purinergic P2X7 receptor drives T cell lineage choice and shapes peripheral gammadelta cells. J Immunol 189(1):174–180. https://doi.org/10.4049/jimmunol.1101582 CrossRefPubMed

77.

Zhao Y, Niu C, Cui J (2018) Gamma-delta (gammadelta) T cells: friend or foe in cancer development? J Transl Med 16(1):3. https://doi.org/10.1186/s12967-017-1378-2 CrossRefPubMedPubMedCentral

78.

Shinohara Y, Tsukimoto M (2017) Adenine nucleotides attenuate murine T cell activation induced by Concanavalin A or T cell receptor stimulation. Front Pharmacol 8:986. https://doi.org/10.3389/fphar.2017.00986 CrossRefPubMed

79.

Trabanelli S, Ocadlikova D, Gulinelli S, Curti A, Salvestrini V, Vieira RP, Idzko M, Di Virgilio F, Ferrari D, Lemoli RM (2012) Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation. J Immunol 189(3):1303–1310. https://doi.org/10.4049/jimmunol.1103800 CrossRefPubMed

80.

Veglia F, Perego M, Gabrilovich D (2018) Myeloid-derived suppressor cells coming of age. Nat Immunol 19(2):108–119. https://doi.org/10.1038/s41590-017-0022-x CrossRefPubMedPubMedCentral

81.

Bianchi G, Vuerich M, Pellegatti P, Marimpietri D, Emionite L, Marigo I, Bronte V, Di Virgilio F, Pistoia V, Raffaghello L (2014) ATP/P2X7 axis modulates myeloid-derived suppressor cell functions in neuroblastoma microenvironment. Cell Death Dis 5:e1135. https://doi.org/10.1038/cddis.2014.109 CrossRefPubMedPubMedCentral

82.

Vijayan D, Young A, Teng MWL, Smyth MJ (2017) Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer 17(12):709–724. https://doi.org/10.1038/nrc.2017.86 CrossRefPubMed

83.

Antonioli L, Pacher P, Vizi ES, Hasko G (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med 19(6):355–367. https://doi.org/10.1016/j.molmed.2013.03.005 CrossRefPubMedPubMedCentral

84.

Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J (2008) Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (review). Int J Oncol 32(3):527–535PubMed

85.

Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204(6):1257–1265. https://doi.org/10.1084/jem.20062512 CrossRefPubMedPubMedCentral

86.

Di Virgilio F, Sarti AC, Falzoni S, De Marchi E, Adinolfi E (2018) Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat Rev Cancer. https://doi.org/10.1038/s41568-018-0037-0 CrossRefPubMed

87.

Tourneur L, Mistou S, Schmitt A, Chiocchia G (2008) Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J Biol Chem 283(26):17929–17938. https://doi.org/10.1074/jbc.M802263200 CrossRefPubMed

88.

Brose KM, Lee AY (2008) Cancer-associated thrombosis: prevention and treatment. Curr Oncol 15(Suppl 1):S58–S67CrossRefPubMedPubMedCentral

89.

Rothmeier AS, Marchese P, Langer F, Kamikubo Y, Schaffner F, Cantor J, Ginsberg MH, Ruggeri ZM, Ruf W (2017) Tissue factor prothrombotic activity is regulated by integrin-arf6 trafficking. Arterioscler Thromb Vasc Biol 37(7):1323–1331. https://doi.org/10.1161/ATVBAHA.117.309315 CrossRefPubMedPubMedCentral

90.

Date K, Ettelaie C, Maraveyas A (2017) Tissue factor-bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer. J Thromb Haemost 15(12):2289–2299. https://doi.org/10.1111/jth.13871 CrossRefPubMed

91.

Crusz SM, Balkwill FR (2015) Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol 12(10):584–596. https://doi.org/10.1038/nrclinonc.2015.105 CrossRefPubMed

92.

Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z (2011) Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 187(2):676–683. https://doi.org/10.4049/jimmunol.1003884 CrossRefPubMed

93.

Morelli A, Chiozzi P, Chiesa A, Ferrari D, Sanz JM, Falzoni S, Pinton P, Rizzuto R, Olson MF, Di Virgilio F (2003) Extracellular ATP causes ROCK I-dependent bleb formation in P2X7-transfected HEK293 cells. Mol Biol Cell 14(7):2655–2664. https://doi.org/10.1091/mbc.02-04-0061 CrossRefPubMedPubMedCentral

94.

Pfeiffer ZA, Aga M, Prabhu U, Watters JJ, Hall DJ, Bertics PJ (2004) The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho. J Leukoc Biol 75(6):1173–1182. https://doi.org/10.1189/jlb.1203648 CrossRefPubMed

95.

Panupinthu N, Zhao L, Possmayer F, Ke HZ, Sims SM, Dixon SJ (2007) P2X7 nucleotide receptors mediate blebbing in osteoblasts through a pathway involving lysophosphatidic acid. J Biol Chem 282(5):3403–3412. https://doi.org/10.1074/jbc.M605620200 CrossRefPubMed

96.

Fairbairn IP, Stober CB, Kumararatne DS, Lammas DA (2001) ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X(7)-dependent process inducing bacterial death by phagosome-lysosome fusion. J Immunol 167(6):3300–3307CrossRefPubMed

97.

Garcia-Marcos M, Dehaye JP, Marino A (2009) Membrane compartments and purinergic signalling: the role of plasma membrane microdomains in the modulation of P2XR-mediated signalling. FEBS J 276(2):330–340. https://doi.org/10.1111/j.1742-4658.2008.06794.x CrossRefPubMed

98.

Skotland T, Sandvig K, Llorente A (2017) Lipids in exosomes: current knowledge and the way forward. Prog Lipid Res 66:30–41. https://doi.org/10.1016/j.plipres.2017.03.001 CrossRefPubMed

99.

Ferrari D, Bianchi N, Eltzschig HK, Gambari R (2016) MicroRNAs modulate the purinergic signaling network. Trends Mol Med 22(10):905–918. https://doi.org/10.1016/j.molmed.2016.08.006 CrossRefPubMed

100.

Graner MW, Schnell S, Olin MR (2018) Tumor-derived exosomes, microRNAs, and cancer immune suppression. Semin Immunopathol. https://doi.org/10.1007/s00281-018-0689-6

101.

Moore C, Kosgodage U, Lange S, Inal JM (2017) The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy. Int J Cancer 141(3):428–436. https://doi.org/10.1002/ijc.30672 CrossRefPubMed

Title: Extracellular vesicles in cancer immune responses: roles of purinergic receptors
Author: Michael W Graner
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 5/2018
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-018-0706-9

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